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Abstract Background The impact of chronic diseases on the patient and the family ranges from minimal to severe distress. Family functioning has been often investigated as a psychosocial measure having an essential role for social adjustment in chronic diseases. Objectives To compare family functioning among families of adolescents with congenital heart disease (CHD) and healthy controls (H) in relation to cohesion, adaptability, and family risk. Method Cross-sectional exposed-control study with 2 groups of adolescents (12 -18 years). The exposed group included adolescents with congenital heart disease (CHD), from a specialized public health system hospital (SUS), and adolescents from 7 public schools, considered healthy, composed the control group. In the hospital, the data collection was individual, before the medical consultation. In schools, the collection took place in groups. Adolescents and parents responded to the FACES III scale. The following statistical tests were used: Pearson's chi-square, Fisher's test, T-test for independent samples, Poisson multivariate regression analysis with 95% reliability, significance established at 5% and a statistical power at 99% (ß = 0.01). Results A total of 161 (41.6%) adolescents with CHD and 226 (58.4%) healthy adolescents participated. There was greater family cohesion among adolescents with CHD, with a higher frequency of connected families, while among healthy adolescents, there are more families of the disengaged type. Regarding adaptability, a higher proportion of families of the chaotic type were found among healthy adolescents compared to adolescents with CHD. A higher frequency of high-risk families was identified among healthy adolescents (16.8%). Conclusion The families of the adolescents with CHD have a more balanced functioning and low risk when compared to the families of healthy adolescents; with greater cohesion between the members and greater adaptability. Congenital heart disease was not an independent factor for high-risk family. (Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0).
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Abstract Objectives: To develop and validate an instrument about nutritional knowledge and feeding practices to be used in children aged 7-11 years, based on the latest Brazilian Food Guide. Methods: Review on the subject; instrument creation; content validity with two groups of judges: first, nutritionists and, after adjustments, a multidisciplinary group (content validity index [CVI]); FACE validity; reproducibility analysis (intraclass correlation coefficient [ICC], level of agreement, and kappa [k]); internal consistency analysis (Cronbach's alpha[α]) and construct validity (Kaiser-Meyer-Olkin and exploratory factorial analysis). The sample was calculated, considering at least ten subjects for each question of the questionnaire. Results: There was a final sample of 453 children (53.6% girls), with a mean age of 9.45 years (SD = 1.44). The content validity showed a CVI ≥ 0.80 for relevance in 62.3% of the items for nutritionists' group and 100% of the items for the multidisciplinary group, clarity (49.4%, 91.8%), and pertinence (58.8%, 98.4%), respectively. The test-retest showed a level of agreement of 84.3% and k = 0.740 for the Knowledge dimension and ICC = 0.754 for the Food Practices dimension. The internal consistency showed α = 0.589 for the Knowledge dimension and α = 0.618 for the Food Practices dimension. For the construct validity, Kaiser-Meyer-Olkin was 0.724 and exploratory factorial analysis showed a variance of 47.01 with varimax rotation and defined five factors for the Practices Dimension. Conclusion: The Food Knowledge and Practices Questionnaire (Questionário de Conhecimento e Práticas Alimentares [QCPA]) instrument showed validity and reliability to assess nutritional knowledge and food practices in children aged 7-11 years.
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Humanos , Feminino , Criança , Conhecimentos, Atitudes e Prática em Saúde , Alimentos , Brasil , Inquéritos e Questionários , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: To develop and validate an instrument about nutritional knowledge and feeding practices to be used in children aged 7-11 years, based on the latest Brazilian Food Guide. METHODS: Review on the subject; instrument creation; content validity with two groups of judges: first, nutritionists and, after adjustments, a multidisciplinary group (content validity index [CVI]); FACE validity; reproducibility analysis (intraclass correlation coefficient [ICC], level of agreement, and kappa [k]); internal consistency analysis (Cronbach's alpha[α]) and construct validity (Kaiser-Meyer-Olkin and exploratory factorial analysis). The sample was calculated, considering at least ten subjects for each question of the questionnaire. RESULTS: There was a final sample of 453 children (53.6% girls), with a mean age of 9.45 years (SDâ¯=â¯1.44). The content validity showed a CVIâ¯≥â¯0.80 for relevance in 62.3% of the items for nutritionists' group and 100% of the items for the multidisciplinary group, clarity (49.4%, 91.8%), and pertinence (58.8%, 98.4%), respectively. The test-retest showed a level of agreement of 84.3% and kâ¯=â¯0.740 for the Knowledge dimension and ICCâ¯=â¯0.754 for the Food Practices dimension. The internal consistency showed αâ¯=â¯0.589 for the Knowledge dimension and αâ¯=â¯0.618 for the Food Practices dimension. For the construct validity, Kaiser-Meyer-Olkin was 0.724 and exploratory factorial analysis showed a variance of 47.01 with varimax rotation and defined five factors for the Practices Dimension. CONCLUSION: The Food Knowledge and Practices Questionnaire (Questionário de Conhecimento e Práticas Alimentares [QCPA]) instrument showed validity and reliability to assess nutritional knowledge and food practices in children aged 7-11 years.
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Alimentos , Conhecimentos, Atitudes e Prática em Saúde , Brasil , Criança , Feminino , Humanos , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The preparation of parents of children who should undergo cardiac surgery requires special treatment such as the explanations about the event. This study aims to compare the effects of standardized nursing guidelines with routine institutional orientation on the anxiety of parents of children undergoing cardiac surgery. METHODS: Randomized clinical trial. The sample consisted of parents of children who underwent cardiac surgery from December 2010 to April 2011. Twenty-two parents were randomized to the intervention group (IG) and received the standard nursing guidelines and 22 participated in the control group (CG) and received the routine guidelines from the institution. Anxiety was assessed by the State-Trait Anxiety Inventory (STAI) applied in the preoperative period, between 12 and 20 hours before surgery and before receiving standard or institutional guidelines and 48 hours after surgery. The analysis of variance (ANOVA) for repeated measures was performed to evaluate the differences between the variations in STAI scores between the groups during the studied period. The level of significance was 0.05. RESULTS: There were no significant differences in baseline anxiety scores between groups with regard to trait anxiety as well as state anxiety: STAI-trait (CG 42.6±4.9 vs. IG 41.4±6.0, P=0.48); STAI-state (CG 42.3±5.7 vs. IG 45.6±8.3, P=0.18). Likewise, the variation in score after 48 hours was similar between groups (STAI-trait P=0.77; STAI-state P=0.61). CONCLUSION: There were no significant differences in the parents' anxiety levels when comparing the two types of guidelines: the standard nursing and the institutional orientation.
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Ansiedade , Procedimentos Cirúrgicos Cardíacos , Humanos , Pais , Guias de Prática Clínica como Assunto , Período Pré-OperatórioRESUMO
Abstract Objective: The preparation of parents of children who should undergo cardiac surgery requires special treatment such as the explanations about the event. This study aims to compare the effects of standardized nursing guidelines with routine institutional orientation on the anxiety of parents of children undergoing cardiac surgery. Methods: Randomized clinical trial. The sample consisted of parents of children who underwent cardiac surgery from December 2010 to April 2011. Twenty-two parents were randomized to the intervention group (IG) and received the standard nursing guidelines and 22 participated in the control group (CG) and received the routine guidelines from the institution. Anxiety was assessed by the State-Trait Anxiety Inventory (STAI) applied in the preoperative period, between 12 and 20 hours before surgery and before receiving standard or institutional guidelines and 48 hours after surgery. The analysis of variance (ANOVA) for repeated measures was performed to evaluate the differences between the variations in STAI scores between the groups during the studied period. The level of significance was 0.05. Results: There were no significant differences in baseline anxiety scores between groups with regard to trait anxiety as well as state anxiety: STAI-trait (CG 42.6±4.9 vs. IG 41.4±6.0, P=0.48); STAI-state (CG 42.3±5.7 vs. IG 45.6±8.3, P=0.18). Likewise, the variation in score after 48 hours was similar between groups (STAI-trait P=0.77; STAI-state P=0.61). Conclusion: There were no significant differences in the parents' anxiety levels when comparing the two types of guidelines: the standard nursing and the institutional orientation.
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Humanos , Ansiedade , Procedimentos Cirúrgicos Cardíacos , Pais , Guias de Prática Clínica como Assunto , Período Pré-OperatórioRESUMO
BACKGROUND: Parental feeding practices may play a key role in dietary habits and nutritional status of adolescents, but research from adolescents' point of view on this topic is scarce. OBJECTIVE: To adapt and validate an instrument of parental feeding practices as perceived by adolescents in a Brazilian setting. METHODS: The Comprehensive Feeding Practices Questionnaire was translated into Portuguese and adapted to be answered by adolescents (ages 12 to 18). Content analysis and FACE validity to assess cultural equivalence was undertaken by experts in the adolescent nutritional and psychological fields. Pilot study was evaluated in 23 adolescents. The final version was administered to 41 students to assess instrument reproducibility (Intraclass Correlation Coefficient). Internal consistency (Cronbach's Alpha) and construct validity (Confirmatory Factor Analysis) were assessed in a third sample of 307 adolescents. RESULTS: Experts and adolescents considered content validity as appropriate. In reproducibility analysis (Intraclass Correlation Coefficient), 10 of the 12 factors were above 0.7. The factors "teaching about nutrition" and "food as reward" obtained values of 0.60 and 0.68, respectively. The Cronbach's Alpha of the whole scale was 0.83 and alphas for subscales ranged from 0.52 to 0.85; the factors "teaching about nutrition" and "food as a reward" had the lowest values (0.52). After removing these two factors, the Confirmatory Factor Analysis indicated that the structural model was appropriate. The final scale was made up of 10 factors with 43 questions. CONCLUSIONS: The Comprehensive Feeding Practices Questionnaire-Teen demonstrates validity and reliability, and is a suitable tool to evaluate the perceptions of adolescents regarding parental feeding practices.
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Dieta , Inquéritos e Questionários , Adolescente , Adulto , Brasil , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: The ocular effects of obesity and hypertension need to be established and can be used as prognostic markers. OBJECTIVE: To estimate the prevalence of ophthalmological alterations in children and adolescents who are overweight and/or have SAH. METHODS: The database for this study included all observational studies (CS, cohort, case-control and "baseline" description of randomized clinical trials) with children and/or adolescents who were overweight, obese or had SAH and that measured ophthalmological alterations. RESULTS: Comparative studies with healthy children demonstrated positive association between body adiposity with retinal venular dilation, and SAH with retinal arteriolar narrowing. Different retinal fundus cameras and computer-assisted programs to evaluate the retinal vessels, variations in the methods of analysis, adjustments, populations, were the main arguments against formal meta-analysis. The heterogeneity was too high (I2 >90%, in fixed or randomized effects), and the lack of linearity, normal distribution and homoscedasticity did not recommend meta-regression. CONCLUSION: Obesity and SAH show associations with ophthalmological alterations, especially with retinal vessel diameter. Lack of standardization does not allow a quantitative evaluation.
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Specific molecular interactions provide a fundamental mechanism for selectivity in every aspect of biological structure and function. The ability to measure quantitatively such interaction properties across a wide range of affinity, size, and purity is a growing need. A short review on the use of the optical biosensor techniques is presented, focused on its application for determining the absorption and distribution parameters of drugs and lead compounds. The basic biosensor technology principles are described together with some immobilization methods commonly used for the preparation of selective and specific biosensor surfaces for assays. Some relevant research topics in the field of small molecule recognition phenomena are presented as examples, including binding to plasma proteins, and binding to lipid membranes, in the frame of ADME (absorption, distribution, metabolism and excretion) parameter determinations. These applications demonstrate the applicability of such techniques to the study of low mass compounds and illustrates their potential for the screening of libraries of compounds with regard to their binding to target bio-molecules as part of drug development.
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Técnicas Biossensoriais , Avaliação Pré-Clínica de Medicamentos , Adsorção , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/tendências , Humanos , Ligantes , Óptica e Fotônica , Ressonância de Plasmônio de Superfície/instrumentaçãoRESUMO
The secondary structure of two synthetic peptides from heptad-repeat domains of herpes simplex virus 1 glycoprotein H was determined by circular dichroism. In particular, the propensity of these peptides to assume an ordered structure was investigated upon by changing the solvent's polarity and the temperature. A reduction of solvent polarity led to a significant increase in the alpha-helix content in the case of HR1, whereas only a slight change in the secondary structure was observed in the case of HR2. In both cases the conformational change followed a two-state transition model. The interaction of the peptides was monitored by the conformational change in the mixture with respect to the single peptides. However, formation of the complex did not significantly enhance thermal stability. A reliable estimation of the secondary structure was obtained by optimising the experimental conditions to collect CD data down to 180 nm, and by comparing the structure data yielded by different software packages.
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Peptídeos/química , Proteínas do Envelope Viral/química , Motivos de Aminoácidos , Dicroísmo Circular , Conformação Proteica , Dobramento de Proteína , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Software , Solventes/química , TemperaturaRESUMO
The aim of this study was to elucidate the vasodilating mechanism of sodium nitroprusside (SNP). To do this, SNP was intravenously infused in pigs (1.67 micromol/kg), and the following paramagnetic metabolites were identified by electron spin resonance: 1) nitrosylhemoglobin [HbFe(II)NO] as an index of the bioconservative pathway; 2) transferrin; 3) [Fe((II))(CN)(5) NO](3-) and [Fe((II))(CN)(4) NO](2-), the reduced penta- and tetracoordinated intermediates of SNP, respectively; and 4) methemoglobin (met-Hb). The results indicate the following: 1) approximately 17% of the dose is converted to HbFe(II)NO at the end of infusion; 2) NO administered as SNP does not undergo bioinactivation (oxidative metabolism), because no significant increase of met-Hb was observed; 3) the equilibrium involving the paramagnetic species of SNP is shifted toward HbFe(II)NO, because a significant increase of transferrin but no detection of the reduced paramagnetic intermediates of SNP was observed. The results obtained indicate that the hemodynamic effect induced by SNP is not mediated by HbFe(II)NO, at least under physiological conditions; hence, a direct release of NO from SNP in the vascular target should be considered. To demonstrate this mechanism, endothelial cells were incubated with SNP, and the release of NO was determined by a novel chemiluminescence method. The results indicate that the endothelium is able to metabolize SNP, with the formation of stoichiometric amounts of NO. In conclusion, SNP is rapidly metabolized to HbFe(II)NO, but the pharmacological response is mediated by a direct mechanism of NO release of the parent compound at the cellular target.
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Medições Luminescentes/métodos , Nitroprussiato/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Espectroscopia de Ressonância de Spin Eletrônica , Células Endoteliais/efeitos dos fármacos , Hemoglobinas/análise , Metemoglobina/análise , Óxido Nítrico/análise , Reprodutibilidade dos Testes , Suínos , Fatores de Tempo , Transferrina/análiseRESUMO
Herpes simplex virus 1 (HSV-1) entry into cells and cell-cell fusion mediated by HSV-1 glycoproteins require four glycoproteins, gD, gB, gH, gL. Of these, gH is the only one that so far exhibits structural-functional features typical of viral fusion glycoproteins, i.e., a candidate fusion peptide and, downstream of it, a heptad repeat (HR) segment able to form a coiled coil, named HR-1. Here, we show that gH carries a functional HR-2 capable of physical interaction with HR-1. Specifically, mutational analysis of gH aimed at increasing or decreasing the ability of HR-2 to form a coiled coil resulted in an increase or decrease of fusion activity, respectively. HSV infection was modified accordingly. A mimetic peptide with the HR-2 sequence inhibited HSV-1 infection in a specific and dose-dependent manner. Circular dichroism spectroscopy showed that both HR-2 and HR-1 mimetic peptides adopt mainly random conformation in aqueous solution, while a decrease in peptide environmental polarity determines a conformational change, with a significant increase of the alpha-helical conformation content, in particular, for the HR-1 peptide. Furthermore, HR-1 and HR-2 mimetic peptides formed a stable complex, as revealed in nondenaturing electrophoresis and by circular dichroism. The mixture of HR-1 and HR-2 peptides reversed the inhibition of HSV infection exerted by the single peptides. Complex formation between HR-1 and HR-2 was independent of the presence of adjacent gH sequences and of additional glycoproteins involved in entry and fusion. Altogether, HR-2 adds to the features typical of class 1 fusion glycoproteins exhibited by HSV-1 gH.
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Motivos de Aminoácidos , Herpesvirus Humano 1/fisiologia , Proteínas do Envelope Viral/fisiologia , Animais , Antígenos de Superfície/análise , Antivirais/farmacologia , Linhagem Celular , Dicroísmo Circular , Cricetinae , Análise Mutacional de DNA , Genes Reporter , Herpesvirus Humano 1/genética , Fusão de Membrana , Conformação Molecular , Mimetismo Molecular , Peptídeos/farmacologia , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , beta-Galactosidase/análise , beta-Galactosidase/genéticaAssuntos
Ácidos Aminossalicílicos/efeitos adversos , Cálculos/etiologia , Doença de Crohn/tratamento farmacológico , Obstrução Intestinal/etiologia , Adulto , Ácidos Aminossalicílicos/uso terapêutico , Cálculos/química , Doença de Crohn/cirurgia , Humanos , Doença Iatrogênica , Obstrução Intestinal/diagnóstico por imagem , Masculino , Radiografia , RecidivaRESUMO
The metabolic fate of nitric oxide (NO) released from nitroaspirin, benzoic acid, 2-(acetyloxy)-3-[(nitrooxy)methyl]phenyl ester (NCX 4016), the lead compound of a new class of NO-releasing non steroidal anti-inflammatory drugs (NO-NSAIDs), has been studied in the rat following p.o. and i.p. administration of 100 mg/kg, by monitoring in plasma the bioactive storage forms of NO (S-nitrosothiols, RS-NO) and its oxidation products (nitrites/nitrates, NOx) by a chemiluminescent assay. In parallel, plasma was analyzed for unchanged drug and metabolites by reverse-phase HPLC. In orally treated rats, no unchanged drug is observed in the 0-24 h interval post-dosing, but only salicylic acid (SA), NOx and RS-NO. The time-course of SA formation parallels that of plasma NOx (plateau after 6 h). Nitrosothiols in plasma are detectable at 1 h, peak at 4 h post-administration, and decline thereafter. The results relative to i.p. administration show a more pronounced and rapid NO delivery (peak of both NOx and RS-NO at 1 h and plateau between 1 and 2 h), still coincident with the peak of SA, and the presence in plasma of NCX 4015 (a metabolite of NCX 4016 which still bears the nitrate function). In myocardial tissue from p.o. treated rats, no drug or metabolites were ever detected, and the NOx levels were always in the range of the controls. Conversely, following i.p. treatment, we observed a rapid compartmentalization within the heart of the unchanged drug, which rapidly disappears in favour of its breakdown products NCX 4015 and SA, with a concomitant rise in myocardial NOx levels up to 2 h. To check the stability of NCX 4016 in the acidic gastric milieu and to explain the different distribution of the drug following p.o. or i.p. administration, the gastric content of the orally-treated animals at different post-dosing times was analysed by HPLC. The unchanged drug was detected up to 8 h post-dosing (levels slowly decreased with time), and the only metabolite to be detected was the O-deacetylated derivative (NCX 4023), which was present in low concentrations up to 4 h post-dosing. This indicates that NCX 4016 does not undergo biotransformation in the upper part of gastrointestinal tract (no direct release of NO in this district) and that the stomach acts as a reservoir for the drug.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Óxido Nítrico/farmacocinética , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Aspirina/análogos & derivados , Aspirina/metabolismo , Cromatografia Líquida de Alta Pressão , Injeções Intraperitoneais , Masculino , Óxido Nítrico/sangue , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
The metabolic fate of nitric oxide (NO) released from nitroaspirin, benzoic acid, 2-(acetyloxy)-3-[(nitrooxy)methyl]phenyl ester (NCX 4016), the lead compound of a new class of NO-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) has been studied in eight healthy male Caucasian subjects following p.o. administration of 1600 mg (single dose), by monitoring at different times in plasma the bioactive storage forms of NO, S-nitrosothiols (RSNO) and its oxidation products (NOx). Plasma levels of NOx and RSNO and urinary levels of NOx were determined by an ozone-based chemiluminescent assay using a sensitive Nitric Oxide Analyzer (LOQ: 10 pmol NO injected). In parallel plasma samples were analyzed by a newly developed LC-MS/MS method for analysis of NCX 4015, the metabolite bearing the nitrate ester function. Using MS/MS with multiple reaction monitoring (MRM) in negative ion mode for NCX 4015 and the internal standard (NCX 4015- 13C-D2) it was possible to detect with sufficient accuracy and precision the metabolite in plasma with a quantification limit of 78.1 ng ml(-1). Concentration versus time profile of plasma NCX 4015 gave a Cmax value of 161.94 +/- 47.4 ng ml(-1) and a tmax 4.5 +/- 1 h. The results indicate that both NOx and RSNO (these last for the first time determined in vivo in man following oral administration of a NO-donor drug) are effective plasma markers of NO release in vivo, the latter being an earlier indicator of NO distribution (tmax 2.0 +/- 0.6 h versus 5.4 +/- 1.2 h).
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Aspirina/análogos & derivados , Aspirina/administração & dosagem , Aspirina/análise , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Administração Oral , Adulto , Aspirina/química , Cromatografia Líquida , Humanos , Medições Luminescentes , Masculino , Espectrometria de MassasRESUMO
The peroxynitrite scavenging ability of Procyanidins from Vitis vinifera L. seeds was studied in homogeneous solution and in human umbilical endothelial cells (EA.hy926 cell line) using 3-morpholinosydnonimine (SIN-1) as peroxynitrite generator. In homogeneous phase procyanidins dose-dependently inhibited 2',7'-dichloro-dihydrofluorescein (DCFH) oxidation induced by SIN-1 with an IC50 value of 0.28 microM. When endothelial cells (EC) were exposed to 5 mM SIN-1, marked morphological alterations indicating a necrotic cell death (cell viability reduced to 16 +/- 2.5%) were observed. Cell damage was suppressed by procyanidins, with a minimal effective concentration of 1 microM (cell morphology and integrity completely recovered at 20 microM). Cellular localization of procyanidins in EC was confirmed using a new staining procedure and site-specific peroxyl radical inducers: AAPH and cumene hydroperoxide (CuOOH). Endothelial cells (EC) pre-incubated with procyanidins (20 microM) and exposed to FeCl3/K3Fe(CN)6 showed a characteristic blue staining, index of a site-specific binding of procyanidins to EC. Procyanidins dose-dependently inhibit the AAPH induced lipid oxidation and reverse the consequent loss of cell viability, but were ineffective when oxidation was driven at intracellular level (CuOOH). This demonstrates that the protective effect is due to their specific binding to the outer surface of EC thus to quench exogenous harmful radicals. Procyanidins dose-dependently relaxed human internal mammary aortic (IMA) rings (with intact endothelium) pre-contracted with norepinephrine (NE), showing a maximal vasorelaxant effect (85 +/- 9%) at 50 microM (catechin: 18 +/- 2% relaxation at 50 microM). This effect was completely abolished when IMA-rings were de-endothelized and when IMA-rings with intact endothelium were pretreated with L-NMMA or with the soluble guanylate cyclase inhibitor, ODQ. Pre-incubation with indomethacin reduces (by almost 50%) the vasodilating effect of procyanidins, indicating the involvement also of a COX-dependent mechanism. This was confirmed in another set of experiments, where procyanidins dose-dependently stimulate the prostacyclin (PGI2) release, reaching a plateau between 25 and 50 microM. Finally, pre-incubation of IMA-rings with procyanidins (from 6.25 to 25 microM) resulted in a dose-dependent prevention of the endothelin-1 (ET-1) vasoconstriction. The ability of procyanidins to prevent peroxynitrite attack to vascular cells, by layering on the surface of coronary EC, and to enhance endothelial NO-synthase-mediated relaxation in IMA rings provide further insight into the molecular mechanisms through which they exert cardioprotective activity in ischemia/reperfusion injury in vivo.